Platelet-derived Growth Factor Selectively Inhibits NR2B-containing N-Methyl-D-aspartate Receptors in CA1 Hippocampal Neurons
| Autor: | Bikram Sidhu, John F. MacDonald, Xuanmao Chen, Catherine H. Trepanier, Aeni Lim, Hongbin Li, Michael A. Beazely |
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| Rok vydání: | 2009 |
| Předmět: |
N-Methylaspartate
Adrenergic receptor Becaplermin Hippocampal formation Biology CREB Hippocampus Receptors N-Methyl-D-Aspartate Biochemistry Neuroprotection Receptor Platelet-Derived Growth Factor beta Phenols Piperidines Animals Rats Wistar Cyclic AMP Response Element-Binding Protein Receptor Molecular Biology Cytoskeleton Protein Kinase C Mitogen-Activated Protein Kinase 1 Neurons Platelet-Derived Growth Factor Mitogen-Activated Protein Kinase 3 Phospholipase C gamma musculoskeletal neural and ocular physiology Mechanisms of Signal Transduction Proto-Oncogene Proteins c-sis Cell Biology Actin cytoskeleton Actins Rats Cell biology nervous system biology.protein NMDA receptor Calcium Platelet-derived growth factor receptor Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 284:8054-8063 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m805384200 |
| Popis: | Platelet-derived growth factor (PDGF) beta receptor activation inhibits N-methyl-d-aspartate (NMDA)-evoked currents in hippocampal and cortical neurons via the activation of phospholipase Cgamma, PKC, the release of intracellular calcium, and a rearrangement of the actin cytoskeleton. In the hippocampus, the majority of NMDA receptors are heteromeric; most are composed of 2 NR1 subunits and 2 NR2A or 2 NR2B subunits. Using NR2B- and NR2A-specific antagonists, we demonstrate that PDGF-BB treatment preferentially inhibits NR2B-containing NMDA receptor currents in CA1 hippocampal neurons and enhances long-term depression in an NR2B subunit-dependent manner. Furthermore, treatment of hippocampal slices or cultures with PDGF-BB decreases the surface localization of NR2B but not of NR2A subunits. PDGFbeta receptors colocalize to a higher degree with NR2B subunits than with NR2A subunits. After neuronal injury, PDGFbeta receptors and PDGF-BB are up-regulated and PDGFbeta receptor activation is neuroprotective against glutamate-induced neuronal damage in cultured neurons. We demonstrate that the neuroprotective effects of PDGF-BB are occluded by the NR2B antagonist, Ro25-6981, and that PDGF-BB promotes NMDA signaling to CREB and ERK1/2. We conclude that PDGFbetaR signaling, by preferentially targeting NR2B receptors, provides an important mechanism for neuroprotection by growth factors in the central nervous system. |
| Databáze: | OpenAIRE |
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